Wei Dengshuai, Sun Yong, Zhu Hu, Fu Qinrui
Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, China.
Maoming People's Hospital, Guangdong 525000, China.
ACS Nano. 2023 Dec 12;17(23):23223-23261. doi: 10.1021/acsnano.3c06019. Epub 2023 Dec 2.
Stimuli-responsive polymers can respond to internal stimuli, such as reactive oxygen species (ROS), glutathione (GSH), and pH, biological stimuli, such as enzymes, and external stimuli, such as lasers and ultrasound, , by changing their hydrophobicity/hydrophilicity, degradability, ionizability, , and thus have been widely used in biomedical applications. Due to the characteristics of the tumor microenvironment (TME), stimuli-responsive polymers that cater specifically to the TME have been extensively used to prepare smart nanovehicles for the targeted delivery of therapeutic and diagnostic agents to tumor tissues. Compared to conventional drug delivery nanosystems, TME-responsive nanosystems have many advantages, such as high sensitivity, broad applicability among different tumors, functional versatility, and improved biosafety. In recent years, a great deal of research has been devoted to engineering efficient stimuli-responsive polymeric nanosystems, and significant improvement has been made to both cancer diagnosis and therapy. In this review, we summarize some recent research advances involving the use of stimuli-responsive polymer nanocarriers in drug delivery, tumor imaging, therapy, and theranostics. Various chemical stimuli will be described in the context of stimuli-responsive nanosystems. Accordingly, the functional chemical groups responsible for the responsiveness and the strategies to incorporate these groups into the polymer will be discussed in detail. With the research on this topic expending at a fast pace, some innovative concepts, such as sequential and cascade drug release, NIR-II imaging, and multifunctional formulations, have emerged as popular strategies for enhanced performance, which will also be included here with up-to-date illustrations. We hope that this review will offer valuable insights for the selection and optimization of stimuli-responsive polymers to help accelerate their future applications in cancer diagnosis and treatment.
刺激响应性聚合物可以对内部刺激(如活性氧(ROS)、谷胱甘肽(GSH)和pH值)、生物刺激(如酶)以及外部刺激(如激光和超声波)作出响应,通过改变其疏水性/亲水性、可降解性、离子化性等,因此已广泛应用于生物医学领域。由于肿瘤微环境(TME)的特点,专门针对TME的刺激响应性聚合物已被广泛用于制备智能纳米载体,用于将治疗和诊断剂靶向递送至肿瘤组织。与传统的药物递送纳米系统相比,TME响应性纳米系统具有许多优点,如高灵敏度、在不同肿瘤中的广泛适用性、功能多样性和提高的生物安全性。近年来,大量研究致力于构建高效的刺激响应性聚合物纳米系统,在癌症诊断和治疗方面都取得了显著进展。在这篇综述中,我们总结了一些近期的研究进展,涉及刺激响应性聚合物纳米载体在药物递送、肿瘤成像、治疗和诊疗一体化中的应用。将在刺激响应性纳米系统的背景下描述各种化学刺激。相应地,将详细讨论负责响应性的功能化学基团以及将这些基团引入聚合物的策略。随着对这一主题的研究快速发展,一些创新概念,如顺序和级联药物释放、近红外二区成像和多功能制剂,已成为提高性能的流行策略,本文也将通过最新的示例对其进行介绍。我们希望这篇综述能为刺激响应性聚合物的选择和优化提供有价值的见解,以帮助加速其在癌症诊断和治疗中的未来应用。
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